The NEU oncogene obtained from rat neuroblastoma induced by a chemical carcinogenic substance was found to encode a protein belonging to the EGF receptor family, and the relationship with which was suggested. Thereafter, an NEU human homologue was isolated and named as ERBB2 or HER2 based on the similarity to an EGF receptor (ERBB). Expression of HER2 in breast cancer, prostate cancer, lung cancer, gastric cancer and the like has been reported and HER2 is considered to be involved in the growth of these cancers.
For example, it has been reported that about 25% of primary prostate cancer is HER2 expression positive, and the percentage increases along with the progression of the cancer (Journal of the National Cancer Institute, Vol. 92, No. 23, pp. 1918-1925 (2000)).
In addition, it is known that the prognosis of patients with HER2 expression is poor in comparison with patients without HER2 expression.
HER2 hardly expresses in normal tissues. Therefore, an HER2 selective therapeutic drug would be cancer selective, with the reduced toxicity or extremely few side effects. This means that an extreme safe and highly versatile treatment method can be provided, which is strikingly different from conventional cancer chemotherapeutic agents. Examples of the HER2 selective therapeutic drug include a tyrosine kinase (phosphorylation enzyme) inhibitor having high selectivity to HER2 and the like.
As a compound inhibiting a receptor-type tyrosine kinase including HER2/EGFR kinase, fused heterocyclic compounds (see, for example, WO97/13771, WO98/02437 and WO00/44728), quinazoline derivatives (see, for example, WO02/02552, WO01/98277, WO03/049740 and WO03/050108), thienopyrimidine derivatives (see, for example, WO03/053446), aromatic azole derivatives (see, for example, WO98/03648, WO01/77107 and WO03/031442), and the like are known. However, there has not been any HER2 kinase inhibitory substance placed on the market heretofore as a therapeutic drug for cancer.
In addition, to use such pharmaceutical agents more effectively for the treatment, it is preferable that the efficacy prediction in patients be available.